Microbial Biotransformation Products of Cyclosporin A

Autor:	MICHAELA KUHNT, FRANCIS BITSCH, JULIEN FRANCE, HANS HOFMANN, JEAN-JACQUES SANGLIER, RENE TRABÉR
Rok vydání:	1996
Předmět:	Pharmacology Bacteria biology Metabolite Fungi Biological activity Metabolism biology.organism_classification chemistry.chemical_compound Metabolic pathway chemistry Biotransformation Biochemistry Cyclosporin a Drug Discovery Cyclosporine Humans Immunosuppressive Agents Cyclophilin
Zdroj:	The Journal of Antibiotics. 49:781-787
ISSN:	1881-1469 0021-8820
DOI:	10.7164/antibiotics.49.781
Popis:	In order to mimic the human metabolic pathway of cyclosporin A (CyA) a total of 28 bacterial and 72 fungal strains was screened for their ability to transform CyA. Among 3 bacteria and 11 fungi, which produced the main human metabolite OL-17 [eta HyMeBmt1]CyA, Actinoplanes sp. (ATCC 53771) achieved the best transformation rate (5.4%). Furthermore, the two N-demethylated minor products [Leu4]CyA (3.2%) and [Leu9]CyA (4.7%) were isolated, both known as minor natural metabolites and the first one also as a human biotransformation product. Microbial conversion of CyA using the actinomycete Sebekia benihana (NRRL 11111) yielded [gamma HyMeLeu4]CyA (35%), [gamma HyLeu4]CyA (4.5%) and [gamma HyMeLeu4, gamma HyMeLeu6]CyA (8.6%). The structures of these derivatives correspond with those of the human metabolic pathway. The related compounds [Nva2]CyA (CyG) and [D-MeSer3]CyA were similarly converted to the corresponding 4-gamma-hydroxylated analogues. None of the biotransformation products showed a better immunosuppressive effect than CyA, although in various cases the cyclophilin binding affinity was comparable to that of CyA.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74900e3506a2134f694ca41507aeb87e https://doi.org/10.7164/antibiotics.49.781 Zobrazit plný text záznamu